RESUMO
INTRODUCTION: Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase. MATERIALS AND METHODS: This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi'an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data. RESULTS: Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration. CONCLUSION: Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.
Assuntos
Incontinência Pigmentar , Humanos , Incontinência Pigmentar/patologia , Incontinência Pigmentar/genética , Lactente , Feminino , Estudos Retrospectivos , Masculino , China , Recém-Nascido , Imageamento por Ressonância Magnética , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Pré-Escolar , População do Leste AsiáticoRESUMO
Incontinentia pigmenti (IP, Bloch-Sulzberger syndrome) is a multisystem disorder which associates specific skin lesions that evolves in four stages, and occasionally, central nervous system, eye, hair, and teeth involvement. Familial (35%) and sporadic (65%) cases are caused by pathogenic variants in the IKBKG gene. Here we report an unusual family, where, in two half-sisters affected by typical IP, molecular genetic analysis identified a likely pathogenic non-sense variant in the IKBKG gene of one of the sisters, the other being not a carrier. The strong clinical conviction motivated further molecular genetic investigations, which led to the characterization of a second variant in this unique family. X chromosome inactivation studies demonstrated the paternal origin of these two de novo variants. For genes with frequent de novo mutations, the coexistence of different pathogenic mutations in the same family is a possibility, and constitutes a challenge for genetic counseling.
Assuntos
Quinase I-kappa B , Incontinência Pigmentar , Mutação , Linhagem , Humanos , Incontinência Pigmentar/genética , Incontinência Pigmentar/patologia , Quinase I-kappa B/genética , Feminino , Mutação/genética , Inativação do Cromossomo X/genética , Masculino , Recidiva , Fenótipo , Predisposição Genética para DoençaRESUMO
Incontinentia pigmenti (IP) is a rare X-linked dominant, male-lethal disorder characterized by pathognomic skin lesions. As described in the literature the typical cutaneous changes follow the pattern of Blaschko's lines and develop in four stages that usually start at birth. Stage 1 is called vesicular, bullous or inflammatory. The vesicles are rapidly filled with eosinophils and thus turn into pustules. Thus, the term "pustular" is relevant to the first phase of IP, and the stage can be considered as "vesiculopustular/inflammatory" to be more precise than "vesicular" or "bullous."
Assuntos
Incontinência Pigmentar , Recém-Nascido , Humanos , Masculino , Incontinência Pigmentar/diagnóstico , Incontinência Pigmentar/patologia , Pele/patologia , Vesícula/patologia , Eosinófilos/patologia , Doenças Raras/patologiaRESUMO
Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that affects skin, hair, teeth, eyes and central nervous system. We present the case of a female patient with mild IP caused by a hypomorphic pathogenic variant of the inhibitor of the kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG) gene. This is the first report of a female IP patient with the hypomorphic variant, NM_001099856.6: c.1423dup, which is causative of anhidrotic ectodermal dysplasia with immune deficiency in males.
Assuntos
Displasia Ectodérmica , Síndromes de Imunodeficiência , Incontinência Pigmentar , Feminino , Humanos , Displasia Ectodérmica/genética , Quinase I-kappa B/genética , Síndromes de Imunodeficiência/genética , Incontinência Pigmentar/diagnóstico , Incontinência Pigmentar/genética , Incontinência Pigmentar/patologia , Mutação , Pele/patologiaRESUMO
De novo somatic mutations are well documented in diseases such as neoplasia but are rarely reported in rare diseases. Hovewer, severe genetic diseases that are not compatible with embryonic development are caused exclusively by deleterious mutations that could only be found as mosaic and not as inherited mutations. We will review here the paradigmatic case of Incontinentia Pigmenti, a rare X-linked dominant disease caused by deficiency of the NEMO (also called IKKgamma) protein, which plays a pivotal role in tissue homeostasis. The loss-of-function mutations of NEMO are embryonically lethal in males while females survive because of unbalanced X-inactivation due to NEMO wild type (WT) expressing cells survival despite of NEMO mutant expressing cells. The few surviving IP males are obligatory mosaic mutants with the typical clinical presentation of IP in female. Indeed, the IP pathogenesis in the female and most likely also in the male somatic mosaics is based on the cellular effects of an impaired NEMO activity, but in the context of the interaction of genetically different cells in the affected tissue, which might underline the inflammatory status.
Assuntos
Quinase I-kappa B/deficiência , Quinase I-kappa B/genética , Incontinência Pigmentar/patologia , Mutação com Perda de Função , Mosaicismo , Humanos , Incontinência Pigmentar/etiologia , Incontinência Pigmentar/metabolismo , MasculinoAssuntos
Citodiagnóstico , Incontinência Pigmentar/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Citodiagnóstico/métodos , Eosinófilos/patologia , Feminino , Humanos , Incontinência Pigmentar/patologia , Lactente , Recém-Nascido , Masculino , Melanócitos/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemAssuntos
Doenças Autoimunes/patologia , Síndrome de Down/patologia , Oftalmopatias/patologia , Predisposição Genética para Doença , Doenças Hereditárias Autoinflamatórias/patologia , Incontinência Pigmentar/patologia , Neoplasias/patologia , Doenças Autoimunes/etiologia , Síndrome de Down/complicações , Oftalmopatias/etiologia , Feminino , Doenças Hereditárias Autoinflamatórias/etiologia , Humanos , Incontinência Pigmentar/complicações , Lactente , Masculino , Neoplasias/etiologia , Linhagem , PrognósticoRESUMO
Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis that is usually lethal in utero in males, though exceptionally they survive very rarely either with Klinefelter syndrome or a somatic mosaicism. We performed genomic analysis of five Japanese IP patients including a rare boy case, all of whom were definite cases with retinopathy. Four patients including the boy revealed the recurrent exon 4-10 deletion in the sole known causative gene IKBKG/NEMO, which was confirmed by various specific PCR techniques. The boy's saliva DNA showed a mosaicism consisting of the deletion and intact alleles, but his blood DNA did not. Relative quantification analysis of the real-time PCR data by ∆∆CT method estimated the mosaicism ratio of the boy's saliva as 45:55 (deletion:intact). A genomic analysis for the recurrent deletion at the nucleotide sequence level has been performed directly using patient's DNA and it has been clarified that the breakpoints are within two MER67B repeats in the intron 3 and downstream of exon 10. This is the first report of the assay for the mosaicism ratio of a male IP case with a recurrent exon 4-10 deletion of IKBKG/NEMO and the sequencing analysis of the breakpoints of the recurrent deletion directly using patient's sample.
Assuntos
Genômica/métodos , Quinase I-kappa B/genética , Incontinência Pigmentar/patologia , Mosaicismo , Doenças Retinianas/patologia , Deleção de Sequência , Pré-Escolar , Éxons , Feminino , Humanos , Incontinência Pigmentar/complicações , Incontinência Pigmentar/genética , Lactente , Japão , Masculino , Linhagem , Doenças Retinianas/complicações , Doenças Retinianas/genéticaAssuntos
Quinase I-kappa B/genética , Incontinência Pigmentar/genética , Análise Mutacional de DNA , Humanos , Incontinência Pigmentar/diagnóstico , Incontinência Pigmentar/patologia , Recém-Nascido , Cariotipagem , Mutação com Perda de Função , Masculino , Índice de Gravidade de Doença , Pele/patologiaRESUMO
INTRODUCTION: Incontinentia pigmenti is a rare genodermatosis of inheritance linked to the Xchromosome that affects tissues derived from ectoderm. The aim of the study is to review, as completely as possible, the cases diagnosed in paediatric patients in two hospitals. MATERIAL AND METHODS: A retrospective cross-sectional study was carried out, using the clinical, analytical, radiological, and genetic data of paediatric patients diagnosed with incontinentia pigmenti from 2004 to 2018. The data collected were analysed and evaluated at a multidisciplinary level. RESULTS: A total of thirteen patients diagnosed with incontinentia pigmenti were included in the study. All of them were female. A genetic study was performed on 11 patients, which confirmed findings compatible with incontinentia pigmenti in 10 of them. Extracutaneous involvement associated with the disease was observed at neurological level (radiological findings in 6 cases, and clinical expression in 3 of them), ophthalmological level (4 cases), dental level (7 cases), and haematological level (4 cases). CONCLUSIONS: A presentation is given of the most complete study published so far of incontinentia pigmenti in Spain. In this study, the results of the disease manifestations were similar to the largest case series published internationally, which reinforces the importance of a multidisciplinary study and follow-up.